Airborne observations of fluorescent aerosol were made aboard an airship during CloudLab, a series of flights that took place in September and October of 2013 and covered a wideband of longitude ...across the continental U.S. between Florida and California and between 28 and 37 N latitudes. Sampling occurred from near the surface to 1000 m above the ground. A Wideband Integrated Bioaerosol Sensor (WIBS‐4) measured average concentrations of supermicron fluorescent particles aloft (1 µm to 10 µm), revealing number concentrations ranging from 2.1 ± 0.8 to 8.7 ± 2.2 × 104 particles m−3 and representing up to 24% of total supermicron particle number. We observed distinct variations in size distributions and fluorescent characteristics in different regions, and attribute these to geographically diverse bioaerosol. Fluorescent aerosol detected in the east is largely consistent with mold spores observed in a laboratory setting, while a shift to larger sizes associated with different fluorescent patterns is observed in the west. Fluorescent bioaerosol loadings in the desert west were as high as those near the Gulf of Mexico, suggesting that bioaerosol is a substantial component of supermicron aerosol both in humid and arid environments. The observations are compared to model fungal and bacterial loading predictions, and good agreement in both particle size and concentrations is observed in the east. In the west, the model underestimated observed concentrations by a factor between 2 and 4 and the prescribed particle sizes are smaller than the observed fluorescent aerosol. A classification scheme for use with WIBS data is also presented.
Key Points
Fluorescent supermicron aerosol loads are reported across the southern U.S.
Regional variations in fluorescent behavior and particle size are observed
Comparison to modeled emissions shows an underestimate in the west
Background
Hybrid natural‐orifice transluminal endoscopic surgery (NOTES), combining access through a natural orifice with small‐sized abdominal trocars, aims to reduce pain and enhance recovery. The ...objective of this systematic review and meta‐analysis was to compare pain and morbidity in hybrid NOTES and standard laparoscopy.
Methods
A systematic literature search was performed to identify RCTs and non‐RCTs comparing hybrid NOTES and standard laparoscopy. The main outcome was pain on postoperative day (POD) 1. Secondary outcomes were pain during the further postsurgical course, rescue analgesia, complications, and satisfaction with the cosmetic result. The results of meta‐analysis in a random‐effects model were presented as odds ratio (ORs) or standard mean differences (MDs) with 95 per cent confidence intervals.
Results
Six RCTs and 21 non‐randomized trials including 2186 patients were identified. In hybrid NOTES the score on the numerical pain scale was lower on POD 1 (−0·75, 95 per cent c.i. −1·09 to −0·42; P = 0·001) and on POD 2–4 (−0·58, −0·91 to −0·26; P < 0·001) than that for standard laparoscopy. The need for rescue analgesia was reduced in hybrid NOTES (OR 0·36, 0·24 to 0·54; P < 0·001). The reduction in complications found for hybrid NOTES compared with standard laparoscopy (OR 0·52, 0·38 to 0·71; P < 0·001) was not significant when only RCTs were considered (OR 0·83, 0·43 to 1·60; P = 0·570). The score for cosmetic satisfaction was higher after NOTES (MD 1·14, 0·57 to 1·71; P < 0·001).
Conclusion
Hybrid NOTES reduces postoperative pain and is associated with greater cosmetic satisfaction in selected patients.
Less pain was the only gain
The goals of this study were to assess the extent of human intestinal drug transporter expression, determine the subcellular localization of the drug uptake transporter OATP1A2, and then to assess ...the effect of grapefruit juice consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1. Expression of drug uptake and efflux transporters was assessed using human duodenal biopsy samples. Fexofenadine uptake by different transporters was measured in a transporter‐transfected cell line. We investigated the influence of grapefruit juice on pharmacokinetics of orally administered fexofenadine. The effect of grapefruit juice on the expression of intestinal transporters was determined using real‐time polymerase chain reaction and Western blot analysis. In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake and efflux transporters was expressed. Importantly, uptake transporters thought to be liver‐specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were expressed in the intestine. However, among OATP transporters, only OATP1A2 was capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice concomitantly or 2 h before fexofenadine administration was associated with reduced oral fexofenadine plasma exposure, whereas intestinal expression of either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug uptake and efflux transporters are expressed in the human intestine. OATP1A2 is likely the key intestinal uptake transporter for fexofenadine absorption whose inhibition results in the grapefruit juice effect. Although short‐term grapefruit juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or MDR1 expression was unaffected.
Clinical Pharmacology & Therapeutics (2007) 81, 362–370. doi: 10.1038/sj.clpt.6100056; published online 10 January 2007
In this chapter, we give an overview of the Graz-BCI research, from the classic motor imagery detection to complex movement intentions decoding. We start by describing the classic motor imagery ...approach, its application in tetraplegic end users, and the significant improvements achieved using coadaptive brain-computer interfaces (BCIs). These strategies have the drawback of not mirroring the way one plans a movement. To achieve a more natural control-and to reduce the training time-the movements decoded by the BCI need to be closely related to the user's intention. Within this natural control, we focus on the kinematic level, where movement direction and hand position or velocity can be decoded from noninvasive recordings. First, we review movement execution decoding studies, where we describe the decoding algorithms, their performance, and associated features. Second, we describe the major findings in movement imagination decoding, where we emphasize the importance of estimating the sources of the discriminative features. Third, we introduce movement target decoding, which could allow the determination of the target without knowing the exact movement-by-movement details. Aside from the kinematic level, we also address the goal level, which contains relevant information on the upcoming action. Focusing on hand-object interaction and action context dependency, we discuss the possible impact of some recent neurophysiological findings in the future of BCI control. Ideally, the goal and the kinematic decoding would allow an appropriate matching of the BCI to the end users' needs, overcoming the limitations of the classic motor imagery approach.
The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in ...these patients.
This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment.
A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups.
CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone.
The last 60 years has seen unprecedented groundwater extraction and overdraft as well as development of new technologies for water treatment that together drive the advance in intentional groundwater ...replenishment known as managed aquifer recharge (MAR). This paper is the first known attempt to quantify the volume of MAR at global scale, and to illustrate the advancement of all the major types of MAR and relate these to research and regulatory advancements. Faced with changing climate and rising intensity of climate extremes, MAR is an increasingly important water management strategy, alongside demand management, to maintain, enhance and secure stressed groundwater systems and to protect and improve water quality. During this time, scientific research—on hydraulic design of facilities, tracer studies, managing clogging, recovery efficiency and water quality changes in aquifers—has underpinned practical improvements in MAR and has had broader benefits in hydrogeology. Recharge wells have greatly accelerated recharge, particularly in urban areas and for mine water management. In recent years, research into governance, operating practices, reliability, economics, risk assessment and public acceptance of MAR has been undertaken. Since the 1960s, implementation of MAR has accelerated at a rate of 5%/year, but is not keeping pace with increasing groundwater extraction. Currently, MAR has reached an estimated 10 km
3
/year, ~2.4% of groundwater extraction in countries reporting MAR (or ~1.0% of global groundwater extraction). MAR is likely to exceed 10% of global extraction, based on experience where MAR is more advanced, to sustain quantity, reliability and quality of water supplies.
Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, ...infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.
MDR1 (P‐glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. ...Single‐strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1ast;2) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1ast;1) or a site‐directed Ser893 mutation (MDR1ast;2) indicated enhanced efflux of digoxin by cells expressing the MDR1‐Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P‐glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1ast;1 and MDR1ast;2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level–time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P‐glycoprotein activity among subjects with the MDR1ast;2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P‐glycoprotein function.
Clinical Pharmacology & Therapeutics (2001) 70, 189–199; doi: 10.1067/mcp.2001.117412
ABSTRACT
We report the discovery of two mini-Neptunes in near 2:1 resonance orbits (P = 7.610303 d for HIP 113103 b and P = 14.245651 d for HIP 113103 c) around the adolescent K-star HIP 113103 (TIC ...121490076). The planet system was first identified from the TESS mission, and was confirmed via additional photometric and spectroscopic observations, including a ∼17.5 h observation for the transits of both planets using ESA CHEOPS. We place ≤4.5 min and ≤2.5 min limits on the absence of transit timing variations over the 3 yr photometric baseline, allowing further constraints on the orbital eccentricities of the system beyond that available from the photometric transit duration alone. With a planetary radius of Rp = $1.829_{-0.067}^{+0.096}$ R⊕, HIP 113103 b resides within the radius gap, and this might provide invaluable information on the formation disparities between super-Earths and mini-Neptunes. Given the larger radius Rp = $2.40_{-0.08}^{+0.10}$ R⊕ for HIP 113103 c, and close proximity of both planets to HIP 113103, it is likely that HIP 113103 b might have lost (or is still losing) its primordial atmosphere. We therefore present simulated atmospheric transmission spectra of both planets using JWST, HST, and Twinkle. It demonstrates a potential metallicity difference (due to differences in their evolution) would be a challenge to detect if the atmospheres are in chemical equilibrium. As one of the brightest multi sub-Neptune planet systems suitable for atmosphere follow up, HIP 113103 b and HIP 113103 c could provide insight on planetary evolution for the sub-Neptune K-star population.
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